• Parasites, Hosts and Diseases
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• 제60권5호
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• pp.317-325
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• 2022

Hypoxia-inducible factor-1 alpha (HIF-1α) is one of the master regulators of immune and metabolic cellular functions. HIF-1α, a transcriptional factor whose activity is closely related to oxygen levels, is a target for understanding infectious disease control. Several studies have demonstrated that HIF-1α plays an important role during the infectious process, while its role in relation to parasite virulence has not been addressed. In this work, we studied the expression levels of HIF-1α and related angiogenic vascular endothelial growth factor A (VEGF-A) in human macrophages infected with promastigotes of hypo- or hyper-virulent Leishmania major human isolates. L. major parasites readily subverted host macrophage functions for their survival and induced local oxygen consumption at the site of infection. In contrast to hypo-virulent parasites that induce high HIF-1α expression levels, hyper-virulent L. major reduced HIF-1α expression in macrophages under normoxic or hypoxic conditions, and consequently impeded the expression of VEGF-A mRNA. HIF-1α may play a key role during control of disease chronicity, severity, or outcome.

• Genomics & Informatics
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• 제20권3호
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• pp.31.1-31.15
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• 2022

A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

• 한국동물생명공학회지
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• 제37권3호
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• pp.183-192
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• 2022

Lipopolysaccharide (LPS) is an endotoxin factor present in the cell wall of Gram-negative bacteria and induces various immune responses to infection. Recent studies have reported that LPS induces cellular stress in various cells including oocytes and embryos. Melatonin (N-acetyl-5-methoxytryptamine) is a regulatory hormone of circadian rhythm and a powerful antioxidant. It has been known that melatonin has an effective function in scavenging oxygen free radicals and has been used as an antioxidant to reduce the cytotoxic effects induced by LPS. However, the effect of melatonin on LPS treated early embryonic development has not yet been confirmed. In this study, we cultured mouse embryos in medium supplemented with LPS or/and melatonin up to the blastocyst stage in vitro and then evaluated the developmental rate. As a result of the LPS-treatment, the rate of blastocyst development was significantly reduced compared to the control group in all the LPS groups. Next, in the melatonin only treated group, there was no statistical difference in embryonic development and no toxic effects were observed. And then we found that the treatment of melatonin improved the rates of compaction and blastocyst development of LPS-treated embryos. In addition, we showed that melatonin treatment decreased ROS levels compared to the LPS only treated group. In conclusion, we demonstrated the protective effect of melatonin on the embryonic developmental rate reduced by LPS. These results suggest a direction to improve reproduction loss that may occur due to LPS exposure and bacterial infection through the using of melatonin during in vitro culture.

• 통합자연과학논문집
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• 제15권3호
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• pp.131-136
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• 2022

Cell migration is essential for diverse cellular processes including wound healing, immune response, development, and cancer metastasis. Pi3-kinase (PI3K) is a key regulator for actin cytoskeleton and phosphorylates phosphatidylinositol (4,5)-diphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3). High levels of PIP3 by PI3Ks are associated with increased levels of F-actin and pseudopod extension at the leading edge of migrating cells such as neutrophils and Dictyostelium. LY294002 is a well-known PI3K specific inhibitor. Here, we investigated the effect of LY294002 on cell migration. First, we evaluated the appropriate concentration of dimethyl sulfoxide (DMSO) for using as a solvent for LY294002. DMSO is a highly polar organic reagent and one of the most common solvent for organic and inorganic chemicals. Cell morphology and cell migration were unaffected at the concentrations less than 0.1 % DMSO. Therefore, stock solution of LY294002 was prepared so that the final concentration of DMSO was 0.1 % or less when treated. When cells were treated with LY294002, cell migration was increased in a concentration-dependent manner. The maximum speed was detected in the presence of 30 µM LY294002. These results suggest that PI3Ks play a inhibitory role in regulating cell migration in our experimental conditions.

• Molecules and Cells
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• 제44권5호
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• pp.281-291
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• 2021

Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.

• Molecules and Cells
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• 제44권7호
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• pp.458-467
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• 2021

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca²⁺ flux via coupling to Gα_i and Gα_q families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gα_q/11 and Gα_12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

• Molecules and Cells
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• 제45권5호
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• pp.317-328
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• 2022

Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported, but little is known about the trophoblast subtypes and distinctive functions during preeclampsia (PE). In this study, we aimed to gain insight into the cell type-specific transcriptomic changes by performing unbiased single-cell RNA sequencing (scRNA-seq) of placental tissue samples, including those of patients diagnosed with PE and matched healthy controls. A total of 29,006 cells were identified in 11 cell types, including trophoblasts and immune cells, and the functions of the trophoblast subtypes in the PE group and the control group were also analyzed. As an important trophoblast subtype, extravillous trophoblasts (EVTs) were further divided into 4 subgroups, and their functions were preliminarily analyzed. We found that some biological processes related to pregnancy, hormone secretion and immunity changed in the PE group. We also identified and analyzed the regulatory network of transcription factors (TFs) identified in the EVTs, among which 3 modules were decreased in the PE group. Then, through in vitro cell experiments, we found that in one of the modules, CEBPB and GTF2B may be involved in EVT dysfunction in PE. In conclusion, our study showed the different transcriptional profiles and regulatory modules in trophoblasts between placentas in the control and PE groups at the single-cell level; these changes may be involved in the pathological process of PE, providing a new molecular theoretical basis for preeclamptic trophoblast dysfunction.

• 한국어병학회지
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• 제35권2호
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• pp.157-165
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• 2022

Single-cycle viruses generated by reverse genetic technology are replication-incompetent viruses due to the elimination of gene(s) essential for viral replication, which provides a way to overcome the safety problem in attenuated viruses. Infectious hematopoietic necrosis virus (IHNV) is a major pathogen causing severe damage in cultured salmonid species. In the present study, we generated a single-cycle IHNV lacking the transmembrane and cytoplasmic domain in the G gene (rIHNV-GΔTM) and evaluated the prophylactic potential of rIHNV-GΔTM in rainbow trout (Oncorhynchus mykiss). To produce rIHNV-GΔTM, IHNV G protein-expressing Epithelioma papulosum cyprini (EPC) cells were established. However, as the efficiency of rIHNV-GΔTM production in EPC cell clones was not high, fish were immunized with a low-tittered single-cycle virus (1.5 × 10² PFU/fish). Despite the low dose, the single-cycle IHNV induced significant protection in rainbow trout against IHNV infection, suggesting high immunogenicity of rIHNV-GΔTM. No significant difference in serum ELISA titers against IHNV between the rIHNV-GΔTM immunized group and the control group suggests that the immunized dose of rIHNV-GΔTM might be too low to induce significant humoral adaptive immune responses in rainbow trout. The involvement of adaptive cellular immunity or innate immunity in the present significantly higher protection by the immunization with rIHNV-GΔTM should be further investigated to know the protection mechanism.

• 운동영양학회지
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• 제25권2호
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• pp.1-7
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• 2021

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis. [Methods] We searched for the existing literature using the keywords such "COVID-19 or microbiota," "microbiota or microRNA," and "COVID-19 or probiotics" in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19. [Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status. [Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

• 한국동물생명공학회지
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• 제37권4호
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• pp.246-254
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• 2022

Current studies have revealed the capacity of mesenchymal stem cells (MSCs) in term of immunomodulatory properties, and this distinct potential is downgraded according to the disease duration of patients-derived MSCs. In order to enhance the immunomodulatory and anti-tumorigenic properties of the rheumatoid arthritis (RA) joints-derived MSCs, we aggregate synovial fluid-derived MSCs from RA joints (RA-hMSCs) into 3D-spheroids by the use of hanging drop culture method. Cells were isolated from synovial fluids of RA joints with longstanding active status over 13 years. For aggregation of RA-hMSCs into 3D-spheroids, cells were plated in hanging drops in 30 μL of advanced DMEM (ADMEM) containing 25,000-30,000 cells/drop and cultured for 48 h. To analyze the comparative immunomodulatory effects of 3D-spheroid and 2D monolayer cultured RA-hMSCs and then cells were cultured in ADMEM supplemented with 20% of synovial fluids of RA patients for 48 h and were evaluated by qRT-PCR for their expression of mRNA levels of inflammatory and anti-inflammatory markers. Cellular aggregation of RA-hMSCs was observed and cells were aggregate into a single sphere. Following treatment of RA patient's synovial fluids into the RA-hMSCs, spheroids formed RA-hMSCs showed significantly (p < 0.05) higher expression of TNFα stimulated gene/protein 6 (TSG-6) than the monolayer cultured RA-hMSCs. Therefore, the 3D-spheroid culture methods of RA-hMSCs were more effective than 2D monolayer cultures in suppressing inflammatory response treated with 20% of RA-synovial fluids by expression of TNFα (TSG-6) according to the immune response and enhanced secretion of inflammatory factors.